TULP1 mutation in two extended Dominican kindreds with autosomal recessive retinitis pigmentosa.
The RP14 autosomal recessive Retinitis pigmentosa (arRP) locus has been mapped to a 2cM region of chromosome 6p21.3. TULP1 (the gene encoding tubby-like protein 1) is a candidate target for the disease mutation because it maps to the RP14 minimum genetic region and because a mutation in the highly homologous mouse tub gene leads to obesity, deafness and early progressive retinal degeneration. Here we report a splice-site mutation (IVS14+1, G-->A) that is homozygous in all affected individuals (N=33) and heterozygous in all obligate carriers (N=50) from two RP14-linked kindreds. The mutation was not observed in 210 unrelated controls. The data indicate that impairment of TULP1 protein function is a rare cause of arRP and that the normal protein plays an essential role in the physiology of the retina.
Banerjee
P
P
Department of Genetics & Development, College of Physicians and Surgeons at Columbia University and New York State Psychiatric Institute, New York 10032, USA.
Kleyn
P W
PW
Knowles
J A
JA
Lewis
C A
CA
Ross
B M
BM
Parano
E
E
Kovats
S G
SG
Lee
J J
JJ
Penchaszadeh
G K
GK
Ott
J
J
Jacobson
S G
SG
Gilliam
T C
TC
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D017931:DNA Primers; D004293:Dominican Republic; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics*
D017931:DNA Primers; D005136:Eye Proteins; C105443:TULP1 protein, human; C491353:Tulp1 protein, mouse